The Clinical Mass Spectrometry Core Lab collaborates with investigators from across the NIDDK Clinical Research Program to conduct stable isotope tracer studies (human and mammalian sources). Clinical studies using stable isotopes involve administering a subject with substances labeled with rare, non-radioactive, stable isotopes, collecting samples, and monitoring production or decay in the isotopic ratio of the labeled product. Stable isotopes are advantageous for clinical studies as they are chemically and physically indistinguishable from the predominant natural isotope of the same element, however, they are readily distinguished and quantitated by isotope ratio mass spectrometers. The most commonly used stable isotopes are hydrogen(2H), oxygen(18O) and carbon(13C) and to a lesser extent nitrogen(15N) and sulfur(34S). The doubly labeled water (DLW) method was developed to measure total energy expenditure. A person or animal is administered a dose of water enriched in deuterium, and 18-oxygen. Labeled hydrogen can only be lost through water, whereas oxygen can be lost as water or carbon dioxide. Calculating the rate of carbon dioxide production then yields a measure of total energy expenditure. Metabolic studies with stable isotopes cover a vast range. Currently we measure labeled glucose, glycerol, and free fatty acids. The lab will advises, develops and validates novel research assays in collaboration with on-going clinical research projects and actively seeks new areas for collaboration with staff from across the NIH community.